Biology subjects

Choi, E.-J.

Publications and source records attributed to Choi, E.-J..

4 recordsLinked to original sources

bioRxiv2023

Pan-cancer analysis reveals multifaceted roles of retrotransposon-fusion RNAs

Transposon-derived transcripts are abundant in RNA sequences, yet their landscape and function, especially for fusion transcripts derived from unannotated or somatically acquired transposons, remains underexplored. Here, we developed a new bioinformatic tool to detect transposon-fusion transcripts in RNA-sequencing data and performed a pan-cancer analysis of 10,257 cancer samples across 34 cancer types as well as 3,088 normal tissue samples. We identified 52,277 cancer-specific fusions with [~]30 events per cancer and hotspot loci within transposons vulnerable to fusion formation. Exonization of intronic transposons was the most prevalent genic fusions, while somatic L1 insertions constituted a small fraction of cancer-specific fusions. Source L1s and HERVs, but not Alus showed decreased DNA methylation in cancer upon fusion formation. Overall cancer-specific L1 fusions were enriched in tumor suppressors while Alu fusions were enriched in oncogenes, including recurrent Alu fusions in EZH2 predictive of patient survival. We also demonstrated that transposon-derived peptides triggered CD8+ T-cell activation to the extent comparable to EBV viruses. Our findings reveal distinct epigenetic and tumorigenic mechanisms underlying transposon fusions across different families and highlight transposons as novel therapeutic targets and the source of potent neoantigens.

cancer biology↗

bioRxiv2021

Changes of small non-coding RNAs by severe acute respiratory syndrome coronavirus 2 infection

The ongoing pandemic of coronavirus disease 2019 (COVID-19), which results from the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a significant global public health threat, with molecular mechanisms underlying its pathogenesis largely unknown. Small non-coding RNAs (sncRNAs) are known to play important roles in almost all biological processes. In the context of viral infections, sncRNAs have been shown to regulate the host responses, viral replication, and host-virus interaction. Compared with other subfamilies of sncRNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), tRNA-derived RNA fragments (tRFs) are relatively new and emerge as a significant regulator of host-virus interactions. Using T4 PNK-RNA-seq, a modified next-generation sequencing (NGS), we recently found that nasopharyngeal swabs (NPS) samples from SARS-CoV-2 positive and negative subjects show a significant difference in sncRNA profiles. There are about 166 SARS-CoV-2-impacted sncRNAs. Among them, tRFs are the most significantly affected and almost all impacted tRFs are derived from the 5-end of tRNAs (tRF5). Using a modified qRT-PCR, which was recently developed to specifically quantify tRF5s by isolating the tRF signals from its corresponding parent tRNA signals, we validated that tRF5s derived from tRNA GluCTC (tRF5-GluCTC), LysCTT (tRF5-LysCTT), ValCAC (tRF5-ValCAC), CysGCA (tRF5-CysGCA) and GlnCTG (tRF5-GlnCTG) are enhanced in NPS samples of SARS-CoV2 patients and SARS-CoV2-infected airway epithelial cells. In addition to host-derived ncRNAs, we also identified several sncRNAs derived from the virus (svRNAs), among which a svRNA derived from CoV2 genomic site 346 to 382 (sv-CoV2-346) has the highest expression. The induction of both tRFs and sv-CoV2-346 has not been reported previously, as the lack of the 3-OH ends of these sncRNAs prevents them to be detected by routine NGS. In summary, our studies demonstrated the involvement of tRFs in COVID-19 and revealed new CoV2 svRNAs.

microbiology↗

bioRxiv2021

MLC Seq: De novo sequencing of full-length tRNA isoforms by mass ladder complementation

tRNAs can exist in distinct isoforms because of different chemical modifications, which confounds attempts to accurately sequence individual tRNA species using next generation sequencing approaches or to quantify different RNA modifications at specific sites on a tRNA strand. Herein, we develop a mass spectrometric (MS) ladder complementation sequencing (MLC-Seq), allowing for direct and simultaneous sequencing of full-length tRNA molecules, including those with low abundance. MLC-seq is achieved by improved instrumentation, and advanced algorithms that identify each tRNA species and related isoforms in an RNA mixture, and assemble full MS ladders from partial ladders with missing ladder components. Using MLC-Seq, we successfully obtained the sequence of tRNA-Phe from yeast and tRNA-Glu from mouse hepatocytes, and simultaneously revealed new tRNA isoforms derived from nucleotide modifications. Importantly, MLC-Seq pinpointed the location and stoichiometry changes of RNA modifications in tRNA-Glu upon the treatment of dealkylated enzyme AlkB, which confirmed its known enzymatic activity and suggested previously unidentified effects in RNA editing.

biochemistry↗

bioRxiv2018

Attenuation of obesity and related metabolic disorders by the individual or combination treatment with IL-2/anti-IL-2 complex and hyperbaric oxygen

Obesity is the disease accumulating excessive fat in the body. The prevalence of obesity and related metabolic disorders is increasing every year worldwide. Immunologically, obesity is a chronic low-grade inflammatory state with the increase of M1 macrophages and decrease of regulatory T cells (Tregs). IL-2/anti-IL-2 complex (IL-2C) and hyperbaric oxygen (HBO) are known to expand Tregs in vivo and suppress inflammation. Therefore, in this study, IL-2C and HBO were investigated for the preventive effect of obesity and related metabolic disorders. Male C57BL/6 mice were fed with a high-fat diet (HFD) for 16 weeks, and counterparts were fed with a low-fat diet (LFD). At the end of the experiment, the body weight gain and impaired glucose metabolism, elevated levels of insulin and total cholesterol induced by HFD were improved by the individual or combination treatment with Il-2C and HBO. Histological examination of the epididymal white adipose tissue showed adipocyte hypertrophy and many crown-like structures in the HFD control groups. In addition, the liver showed the progression of non-alcoholic fatty liver disease (NAFLD) in the HFD control groups, but it was significantly improved by the individual or combination treatment with IL-2C and HBO.\n\nAs for the underlying mechanism, inflammation induced by obesity was decreased, and HIF-1 expression by adipocyte hypertrophy was also reduced by the individual or combination treatment with IL-2C and HBO. In addition, adipose tissue browning was activated in brown and inguinal adipose tissue, and the expression of UCP-1 involved in the thermogenesis was increased by the individual or combination treatment with IL-2C and HBO. Overall, these results suggested that IL-2C and HBO might be a new promising immunotherapy for the treatment of obesity and related metabolic disorders by regulation of inflammation and activation of adipose tissue browning.

immunology↗